This is the second revision of our application to renew the Harvard Older Americans Independence Center (OAIC), which was previously funded by a P60 mechanism for 15 years. Over the past funding cycle our research has shown important relationships between cardiovascular risk factors, the development of cerebral and systemic microvascular disease, and the ultimate development of impaired cognitive and physical functions in older adults. Building on these observations, our renewal will focus on the vascular role In age related functional loss. The overarching goal of the new Harvard OAIC is to strengthen and expand our expertise, scientific resources, and translational research at the interface of vascular medicine and gerontology in order to enhance our understanding of the vascular role in age-related physical and cognitive functional decline, design new interventions to ameliorate this decline, and train new investigators to become skilled in this important area of research. To achieve this goal we are proposing a Research Career Development Core (RCDC) led by Drs. Edward Marcantonio and Murray Mittleman;a Pilot/Exploratory Studies Core (PESC) led by Drs. Douglas Kiel and Anthony Rosenzweig;a Leadership and Administration Core (LAC) led by Drs. Lewis Lipsitz and Peter Oettgen;and 3 Resource Cores, including: 1) Clinical Research and Recruitment, led by Dr. Lewis Lipsitz;2) Advanced Statistics and Psychometrics led by Drs. Richard Jones and Adrienne Cupples;and 3) Physiologic Measurement and Biomarkers led by Dr. Vera Novak. For the RCDC, PESC, and LAC we have created leadership pairs who bring expertise in vascular biology, aging, and mentoring to our OAIC. Dr. Lipsitz Professor of Medicine and founding member of the Harvard OAIC, will continue to serve as principal investigator. After a formal solicitation and review process, we selected 3 RCD, 3 pilot, 2 small pilot, and 12 external projects for support. These are closely allied with our theme, have strong potential for future funding address knowledge gaps in our conceptual model, and bring new expertise to our Pepper Center in endothelial precursor cell biology, adipokine and obesity research, retinal vascular image analysis, endothelial function measurement, renin angiotensin physiology, proteomics, informatics, and nonlinear analysis of dynamic cardiovascular signals. The Harvard OAIC will bring faculty members together for research seminars, cultural competence training, and scientific suppers, and will foster the career development of a diverse group of new scientists who are dedicated to translational research in vascular aging. Our strong institutional commitments, outstanding faculty, extensive resources, and pipeline of talented trainees and junior faculty will help ensure we meet our goals. PUBLIC HEALTH RELEVANCE: Aging is one of the major risk factors for vascular diseases such as coronary heart disease, heart failure, and stroke, which are leading causes of death and disability in elderly people. The Harvard OAIC will strengthen and expand our knowledge and scientific resources in vascular medicine and aging to help us better understand the vascular role in age-related physical and cognitive decline, design new interventions to ameliorate this decline, and train new investigators to study this critical problem.